In vivo release of titanium-containing nanoparticles from 3D-printed hydroxyapatite-coated implants using single-particle inductively coupled plasma mass spectrometry.

Titanium alloys have emerged as the primary material for orthopedic implants, particularly with the advent of 3D-printing technology that has revolutionized the fabrication of complex, biomimetic porous structures. However, the potential release of wear particles poses a critical safety concern, and due to the relatively short clinical history of these novel implants, in vivo data evaluating their safety profile is still limited. Herein, this study established a single-particle inductively coupled plasma mass spectrometry (SP-ICP-MS) method to quantify low-concentration Ti-containing nanoparticles (Ti-NPs) and total Ti in peri-implant tissues, blood, and major organs of rabbits at 1, 2, 3, and 4 months following implantation. A split-body design was utilized to compare HA-coated and uncoated 3D-printed Ti-6Al-4V implants. The results showed that Ti-containing nanoparticles (Ti-NPs) were detected across all peri-implant tissues, blood, and major organs, with the majority being nanosized (<100 nm). In the peri-implant tissues, the Ti-NPs exhibited smaller sizes and lower concentrations in the HA-coated group compared to the uncoated group, demonstrating the protective barrier effect of the coating. Furthermore, the release profile showed that ionic titanium was the dominant species (Ti-NPs <10%), with a distinct systemic distribution pattern. Specifically, by the fourth month, total Ti concentrations in organs decreased sharply due to excretion, whereas Ti-NPs conversely accumulated, with the spleen identified as the primary reservoir. Overall, this work provides important evidence and offers useful guidance for the safety evaluation of 3D-printed implants.